Tissue-type plasminogen activator (t-PA), a key enzyme in the thrombolytic system, is endogenously synthesized as a single chain molecule. However, it can be easily converted into two chains by limited proteolytic cleavage with plasmin or trypsin at the amino acid 275-276 site. The light (L) chain, extending toward the C-terminal part of the molecule, contains the catalytic domain. The heavy (H) chain contains three domains identified as the finger (F) domain, the epidermal growth factor (EGF) domain and two kringle (K1 and K2) sequences. Several studies have suggested that fibrin binding specificity, which fixes t-PA to a thrombus in proximity to plasminogen, resides in the F and K domains of the H-chain. Zonneveld et al., Proc. Natl. Acad. Sci. 83 4670 (1986); Vehar et al., Bio/Technology (Dec.) pp. 1051-1062 (1984) and Patthy, Cell, 41 657 (1985).